PRINCIPLES OF TOXICOLOGY

202 IMMUNOTOXICITY: TOXIC EFFECTS ON THE IMMUNE SYSTEM
Some classes of chemicals or agents have, in particular, been associated with immunotoxic effects
in humans. These are discussed briefly below.
Metals
Metals have been associated with various types of hypersensitivity reactions. Beryllium, nickel,
chromium, cadmium, silver, and zirconium have all been found to produce contact dermatitis. Nearly
10 percent of women and 2 percent of men have sensitivity to nickel, and may develop rashes upon
contact with nickel in jewelry, coins, and clothing fasteners. Sensitive individuals may also respond to
chromium in tanned leather products. Metals are also associated with pulmonary hypersensitivity
reactions and occupational asthma. One of the most serious of these diseases is berylliosis, a delayed
hypersensitivity (type IV) reaction thought to result from beryllium acting as a hapten. Acutely,
hypersensitivity to beryllium is manifested as pneumonitis and pulmonary edema. Chronically,
workers exposed to beryllium develop a severe, debilitating granulomatous lung disease.
Studies in experimental animals have shown that metals such as lead, mercury, nickel, and cadmium
are associated with activation of CD4 + T cells or cause suppression of antibody responses and
cell-mediated immunity, resulting in increased susceptibility to infection. There is some clinical and
epidemiologic evidence that lead may decrease resistance to infectious disease, and the use of arsenic
for medicinal purposes suggests that it, too, may have immunosuppressive effects. Arsenic was used
in the early twentieth century to treat some inflammatory diseases, and currently appears to have some
efficacy in treating leukemia. Also, patients treated with arsenicals were reported to have a relatively
high incidence of the viral disease herpes zoster, suggesting some impairment of the immune system.
A number of studies have reported increased or unusual autoantibodies in association with exposure
to some metals in the workplace, suggesting potential autoimmune toxicity. For example, there is
evidence of immune complex glomerulonephritis in nephrotoxicity from cadmium and mercury. Iodine
and lithium have been linked to autoimmune thyroid disease, and chromium and gold have been
associated with systemic lupus erythematosus-like disease.
Polychlorinated Dibenzo(p)dioxins
Studies in rodents have shown that perinatal exposure to 2,3,7,8-tetrachlorodibenzodioxin (TCDD)
appears to affect the developing thymus, leading to a persistent suppression of cellular immunity. The
depression of T-cell function from perinatal exposure appears to be greater and more persistent than
when exposure occurs in adults. The potential for TCDD immunotoxicity in humans is less clear.
Individuals exposed to very high TCDD doses during an industrial explosion in Seveso, Italy in 1976
have not shown demonstrable loss of immune function. Studies of individuals exposed to TCDD
chronically in Times Beach, Missouri have revealed a few differences from a control population in
some parameters, but overall the observations do not suggest significantly altered immunocompetence.
These studies have focused on humans exposed as adults to TCDD, and it is possible that perinatal
exposure to TCDD may have more profound effects, as has been observed in laboratory animals.
Increased antinuclear antibodies and immune complexes have been reported in blood of dioxinexposed
workers, but increases in clinical manifestations of autoimmunity have not been observed.
Dusts and Particulates
A number of occupations involve inhalation exposure to high-molecular-weight organic molecules or
particles containing these molecules. Examples include flour and wood dust; enzymes (e.g., from B.
subtilis and A. niger in the detergent industry); dusts from agricultural wastes; fungi and bacteria in
moldy hay, feeds, and wood products; and dander, feces, pupae, and other residue from insect and
rodent pests. These high-molecular-weight substances are capable of producing an IgE-mediated, type
I allergic reaction. This reaction can manifest itself as eye and upper respiratory tract congestion,
occupational asthma, and hypersensitivity pneumonitis. Acute inhalation of dusts from bacterial or